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imipenem/cilastatin (i-me-pen-em/sye-la-stat-in) Primaxin
Indications
Treatment of: Lower respiratory tract infections, Urinary
tract infections, Abdominal infections, Gynecologic
infections, Skin and skin structure infections, Bone and
joint infections, Bacteremia, Endocarditis, Polymicrobic
infections.
Action
Imipenem binds to the bacterial cell wall, resulting in
cell death. Combination with cilastatin prevents renal
inactivation of imipenem, resulting in high urinary concentrations.
Imipenem resists the actions of many enzymes
that degrade most other penicillins and penicillin-
like anti-infectives. Therapeutic Effects:
Bactericidal action against susceptible bacteria. Spectrum:
Spectrum is broad. Active against most grampositive
aerobic cocci: Streptococcus pneumoniae,
Group A beta-hemolytic streptococci, Enterococcus,
Staphylococcus aureus. Active against many gram-negative
bacillary organisms: Escherichia coli, Klebsiella,
Acinetobacter, Proteus, Serratia, Pseudomonas aeruginosa.
Also displays activity against: Salmonella,
Shigella, Neisseria gonorrhoeae, Numerous anaerobes.
Pharmacokinetics
Absorption: Well absorbed after IM administration
(imipenem 95%, cilastatin 75%). IV administration results
in complete bioavailability.
Distribution: Widely distributed. Crosses the placenta;
enters breast milk.
Metabolism and Excretion: Imipenem and cilastatin
—70% excreted unchanged by the kidneys.
Half-life: Imipenem and cilastatin—1 hr (qin renal
impairment).
TIME/ACTION PROFILE (blood levels)
ROUTE ONSET PEAK DURATION
IM rapid 1–2 hr 12 hr
IV rapid end of infusion
6–8 hr
Contraindications/Precautions
Contraindicated in: Hypersensitivity; Cross-sensitivity
may occur with penicillins and cephalosporins.
Use Cautiously in: Previous history of multiple hypersensitivity
reactions; Seizure disorders; Renal impairment
(doseprequired if CCr 70 mL/min/1.73
m2); OB, Lactation, Pedi: Safety not established; Geri:
May be atqrisk for toxic reactions due to age-related
qin renal function.
Adverse Reactions/Side Effects
CNS: SEIZURES, dizziness, somnolence. CV: hypotension.
GI: CLOSTRIDIUM DIFFICILE-ASSOCIATED DIARRHEA
(CDAD), diarrhea, nausea, vomiting. Derm: rash,
pruritus, sweating, urticaria. Hemat: eosinophilia.
Local: phlebitis at IV site. Misc: allergic reaction including
ANAPHYLAXIS, fever, superinfection.
Interactions
Drug-Drug: Do not admix with aminoglycosides
(inactivation may occur). Probenecidprenal excretion
andqblood levels.qrisk of seizures with ganciclovir
or cyclosporine (avoid concurrent use of ganciclovir).
Maypserum valproate levels (qrisk of
seizures).
Route/Dosage
IV (Adults): Mild infections—250–500 mg q 6 hr.
Moderate infections—500 mg q 6–8 hr or 1 g q 8
hr. Serious infections—500 mg q 6 hr to 1 g q 6–8
hr.
IV (Children 3 mo [non-CNS infections]): 15–
25 mg/kg q 6 hr; higher doses have been used in older
children with cystic fibrosis.
IV (Children 4 wk–3 mo): 25 mg/kg q 6 hr.
IV (Children 1–4 wk): 25 mg/kg q 8 hr.
IV (Children 1 wk): 25 mg/kg q 12 hr.
IM (Adults): 500–750 mg q 12 hr.
IM (Children): 10–15 mg/kg q 6 hr.
Renal Impairment
IV (Adults): If dose for normal renal function is 1
g/day CCr 41–70 mL/min—125–250 mg q 6–8 hr,
CCr 21–40 mL/min—125–250 mg q 8–12 hr, CCr
6–20 mL/min—125–250 mg q 12 hr; if dose for
normal renal function is 1.5 g/day CCr 41–70 mL/
min—125–250 mg q 6–8 hr, CCr 21–40 mL/
min—125–250 mg q 8–12 hr, CCr 6–20 mL/
min—125–250 mg q 12 hr; if dose for normal renal
function is 2 g/day CCr 41–70 mL/min—125–
500 mg q 6–8 hr, CCr 21–40 mL/min—125–250
mg q 8–12 hr, CCr 6–20 mL/min—125–250 mg q
12 hr; if dose for normal renal function is 3 g/day
CCr 41–70 mL/min—250–500 mg q 6–8 hr, CCr
21–40 mL/min—250–500 mg q 6–8 hr, CCr 6–20
mL/min—250–500 mg q 12 hr; if dose for normal
renal function is 4 g/day CCr 41–70 mL/min—
250–750 mg q 6–8 hr, CCr 21–40 mL/min—250–
500 mg q 6–8 hr, CCr 6–20 mL/min—250–250 mg
q 12 hr.
Availability (generic available)
Powder for IV injection: 250 mg imipenem/250 mg
cilastatin, 500 mg imipenem/500 mg cilastatin. Powder
for IM injection: 500 mg imipenem/500 mg cilastatin,
750 mg imipenem/750 mg cilastatin.
imatinib (i-mat-i-nib) Gleevec
Indications
Newly diagnosed Philadelphia positive (Ph)
chronic myeloid leukemia (CML). CML in blast crisis,
accelerated phase, or in chronic phase after failure of
interferon-alpha treatment. Kit (CD117) positive
metastatic/unresectable malignant gastrointestinal stomal
tumors (GIST). Adjuvant treatment following resection
of Kit (CD117) positive GIST. Pediatric patients
with Ph CML after failure of bone marrow transplant
or resistance to interferon-alpha. Adult patients with
relapsed or refractory Ph acute lymphoblastic leukemia
(ALL). Newly diagnosed Ph ALL (in combination
with chemotherapy). Myelodysplastic/myeloproliferative
disease (MDS/MPD) associated with
platelet-derived growth factor receptor (PDGFR) gene
re-arrangements. Aggressive systemic mastocytosis
(ASM) without the D816V c-Kit mutation or with c-Kit
mutational status unknown. Hypereosinophilic syndrome
and/or chronic eosinophilic leukemia (HES/
CEL). Unresectable, recurrent, or metastatic dermatofibrosarcoma
protuberans (DFSP).
Action
Inhibits kinases which may be produced by malignant
cell lines. Therapeutic Effects: Inhibits production
of malignant cell lines with decreased proliferation of
leukemic cells in CML, HES/CEL, and ALL and malignant
cells in GIST, MDS/MPD, ASM, and DFSP.
Pharmacokinetics
Absorption: Well absorbed (98%) following oral
administration.
Distribution: Unknown.
Protein Binding: 95%.
Metabolism and Excretion: Mostly metabolized
by the CYP3A4 enzyme system to N-demethyl imatinib,
which is as active as imatinib. Excreted mostly in feces
as metabolites. 5% excreted unchanged in urine.
Half-life: Imatinib—18 hr; N-desmethyl imatinib—
40 hr.
TIME/ACTION PROFILE (blood levels of
imatinib)
ROUTE ONSET PEAK DURATION
PO unknown 2–4 hr 24 hr
Contraindications/Precautions
Contraindicated in: Hypersensitivity; OB: Potential
for fetal harm; Lactation: Potential for serious adverse
reactions in nursing infants; breast feeding should be
avoided.
Use Cautiously in: Hepatic impairment (dosep
recommended if bilirubin 3 times normal or liver
transaminases 5 times normal); Cardiac disease (severe
HF and left ventricular dysfunction may occur);
Rep: Women of reproductive potential; Pedi: Children
1 yr (safety not established); Geri:qrisk of edema.
Adverse Reactions/Side Effects
CNS: fatigue, headache, weakness, dizziness, somnolence.
CV: HF. EENT: epistaxis, nasopharyngitis,
blurred vision. Resp: cough, dyspnea, pneumonia.
GI: HEPATOTOXICITY, abdominal pain, anorexia, constipation, diarrhea, dyspepsia, nausea, vomiting. Derm:
DRUG RASH WITH EOSINOPHILIA AND SYSTEMIC SYMPTOMS
(DRESS), petechiae, pruritus, skin rash. F and E:
edema (including pleural effusion, pericardial infusion,
pulmonary edema, and superficial edema), hypokalemia.
Endo:pgrowth (in children), hypothyroidism.
Hemat: BLEEDING, NEUTROPENIA, THROMBOCYTOPENIA.
Metab: weight gain. MS: arthralgia, muscle cramps,
musculoskeletal pain, myalgia. Misc: TUMOR LYSIS SYNDROME,
fever, night sweats.
Interactions
Drug-Drug: Blood levels and effects areqby concurrent
use of potent CYP3A4 inhibitors (e.g. ketoconazole,
itraconazole, clarithromycin, atazanavir,
indinavir, nefazodone, nelfinavir, ritonavir, saquinavir,
or voriconazole). Blood levels and effects
may bepby potent CYP3A4 inducers (e.g., dexamethasone,
phenytoin, carbamazepine, rifampin, rifabutin,
and phenobarbital; if used concurrently,q
dose of imatinib by 50%.qblood levels of simvastatin.
Imatinib inhibits the following enzyme systems:
CYP2C9, CYP2D6, CYP3A4/5 and may be expected to alter
the effects of other drugs metabolized by these systems.
Drug-Food: Blood levels and effects areqby grapefruit
juice; concurrent use should be avoided.
Route/Dosage
Chronic Myeloid Leukemia
PO (Adults): Chronic phase—400 mg once daily,
may beqto 600 mg once daily; accelerated phase or
blast crisis—600 mg once daily; may beqto 800 mg/
day given as 400 mg twice daily based on response and
circumstances.
PO (Children): Newly diagnosed Ph CML—340
mg/m2 once daily (not to exceed 600 mg); CML recurrent
after failure of bone marrow transplant or resistance
to interferon-alpha—260 mg/m2 once daily.
Gastrointestinal Stromal Tumors
PO (Adults): Metastatic or unresectable—400 mg
once daily; may beqto 400 mg twice daily if well tolerated
and response insufficient; Adjuvant treatment after
resection—400 mg once daily.
Ph Acute Lymphoblastic Leukemia
PO (Adults): 600 mg once daily.
PO (Children): 340 mg/m2 once daily (not to exceed
600 mg).
Myelodysplastic/Myeloproliferative Diseases
PO (Adults): 400 mg once daily.
Aggressive Systemic Mastocytosis
PO (Adults): 400 mg once daily. For patients with
eosinophilia—100 mg once daily;qto 400 mg once
daily if well tolerated and response insufficient.
Hypereosinophilic Syndrome and/or
Chronic Eosinophilic Leukemia
PO (Adults): 400 mg once daily. For patients with
FIP1L1–PDGFRa fusion kinase 100 mg once daily;q
to 400 mg once daily if well tolerated and response insufficient.
Dermatofibrosarcoma Protuberans
PO (Adults): 400 mg twice daily.
Hepatic Impairment
PO (Adults):pdose by 25% in severe hepatic impairment.
Renal Impairment
PO (Adults): CCr 40–59 mL/min—Do not exceed
dose of 600 mg/day; CCr 20–39 mL/min—pinitial
dose by 50%;qas tolerated.
Availability (generic available)
Tablets: 100 mg, 400 mg.
iloperidone (eye-loe-per-i-done) Fanapt
Indications
Schizophrenia.
Action
May act by antagonizing dopamine and serotonin in the
CNS. Therapeutic Effects: Decreased symptoms of
schizophrenia.
Pharmacokinetics
Absorption: Well absorbed (96%) following oral
administration.
Distribution: Unknown.
Metabolism and Excretion: Extensively metabolized
by the liver. Metabolism is genetically determined;
primarily by CYP3A4 and CYP2D6 enzyme systems,
with individual variability in metabolism via
CYP2D6 (extensive metabolizers [EM] and poor metabolizers
[PM] and some in-between; 7–10% of Caucasians
and 3–8% of Black/African Americans are considered
PM). Two major metabolites (P88 and P95)
may be partially responsible for pharmacologic activity.
58% excreted in urine as metabolites in EM and 45% in
PM; 20% eliminated in feces in EM and 22.1% in PM.
Half-life: EMs—iloperidone–18 hr, P88–26 hr,
P95–23 hr; PMs—iloperidone–33 hr, P88–37 hr,
P95–31 hr.
TIME/ACTION PROFILE (antipsychotic effect)
ROUTE ONSET PEAK DURATION
PO 2–4 wk 2–4 hr† unknown
† Blood level.
Contraindications/Precautions
Contraindicated in: Hypersensitivity; Concurrent
use of drugs known to prolong QTc interval; Bradycardia,
recent MI or uncompensated heart failure (qrisk
of serious arrhythmias); Congenital long QT syndrome,
QTc interval 500 msec or history of cardiac arrhythmias;
Electrolyte abnormalities, especially hypomagnesemia
or hypokalemia (correct prior to therapy); Severe
hepatic impairment; Lactation: Breast feeding
should be avoided.
Use Cautiously in: Known cardiovascular disease
including heart failure, history of MI/ischemia, conduction
abnormalities, cerebrovascular disease, or other
conditions known to predispose to hypotension including
dehydration, hypovolemia, concurrent antihypertensive
therapy (qrisk of orthostatic hypotension);
Concurrent use of CYP3A4 or CYP2D6 inhibitors;
KnownpWBC or history of drug-induced leukopenia/
neutropenia; Circumstances that may result inqbody
temperature, including strenuous exercise, exposure to
extreme heat, concurrent anticholinergic activity, or dehydration
(may impair thermoregulation); Patients at
risk for aspiration or falls; Moderate hepatic impairment;
OB: Neonates atqrisk for extrapyramidal symptoms
and withdrawal after delivery when exposed during
the 3rd trimester; use only if potential maternal
benefit justifies potential fetal risk; Pedi: Safety and effectiveness
not established; Geri: Elderly patients with
dementia-related psychoses (qrisk of death, CVA or
TIA).
Adverse Reactions/Side Effects
CNS: NEUROLEPTIC MALIGNANT SYNDROME, SUICIDAL
THOUGHTS, dizziness, drowsiness, fatigue, agitation, delusion,
restlessness, extrapyramidal disorders. EENT:
nasal congestion. CV: orthostatic hypotension, tachycardia,
palpitations, QTc interval prolongation. GI: dry
mouth, nausea, abdominal discomfort, diarrhea. GU:
priapism, urinary incontinence. Endo: dyslipidemia,
hyperglycemia, hyperprolactinemia. Neuro: tardive
dyskinesia. Metab: weight gain, weight loss. MS:p
bone density, musculoskeletal stiffness. Misc: ANAPHYLAXIS,
ANGIOEDEMA.
Interactions
Drug-Drug: Avoid use of drugs known to the prolong
QTc interval including the quinidine, procainamide,
amiodarone, sotalol, chlorpromazine,
thioridazine, moxifloxacin, pentamidine, and
methadone. Concurrent use of strong CYP2D6 inhibitors
including fluoxetine and paroxetineqlevels
and the risk of toxicity; dosepis required. Concurrent
use of strong CYP3A4 inhibitors including
ketoconazole and clarithromycinqlevels and the
risk of toxicity; dosagepis required. Concurrent use of
antihypertensives including diuretics mayqrisk of
orthostatic hypotension. Concurrent anticholinergics
mayqrisk of impaired thermoregulation.
Route/Dosage
PO (Adults): Initiate treatment with 1 mg twice daily
on the first day, then 2 mg twice daily the second day,
thenqby 2 mg/day every day until a target dose of 12–
24 mg/day given in two divided doses is reached; Concurrent
strong CYP2D6 or CYP3A4 inhibitors—p
dose by 50%, if inhibitor is withdrawnqdose to previous
amount. Re-titration is required if iloperidone is
discontinued 300 days; Poor metabolizers of
CYP2D6—pdose by 50%.
Availability
Tablets: 1 mg, 2 mg, 4 mg, 6 mg, 8 mg, 10 mg, 12 mg.
ifosfamide (eye-foss-fam-ide) Ifex
Indications
Germ cell testicular carcinoma (with other agents).
Used with mesna, which prevents ifosfamide-induced
hemorrhagic cystitis.
Action
Following conversion to active compounds, interferes
with DNA replication and RNA transcription, ultimately
disrupting protein synthesis (cell-cycle phase–nonspecific).
Therapeutic Effects: Death of rapidly replicating
cells, particularly malignant ones.
Pharmacokinetics
Absorption: Administered IV only; inactive prior to
conversion to metabolites.
Distribution: Excreted in breast milk.
Metabolism and Excretion: Metabolized by the
liver to active antineoplastic compounds.
Half-life: 15 hr.
TIME/ACTION PROFILE (effects on blood
counts)
ROUTE ONSET PEAK DURATION
IV unknown 7–14 days 21 days
Contraindications/Precautions
Contraindicated in: Hypersensitivity; OB, Lactation:
Pregnancy or lactation.
Use Cautiously in: Patients with childbearing potential;
Active infections;pbone marrow reserve; Geri:
Geriatric patients; Other chronic debilitating illness; Renal
impairment; Pedi: Children.
Adverse Reactions/Side Effects
CNS: CNS toxicity (somnolence, confusion, hallucinations,
coma), cranial nerve dysfunction, disorientation,
dizziness. CV: cardiotoxicity. GI: nausea, vomiting, anorexia,
constipation, diarrhea, hepatotoxicity. GU:
hemorrhagic cystitis, dysuria, sterility, renal toxicity.
Derm: alopecia. Hemat: ANEMIA, LEUKOPENIA,
THROMBOCYTOPENIA. Local: phlebitis. Misc: allergic
reactions.
Interactions
Drug-Drug: CYP3A4 inhibitors, including ketoconazole,
fluconazole, itraconazole, sorafenib,
and aprepitant maypits effectiveness. CYP3A4 inducers,
including carbamazepine, phenytoin, phenytoin,
phenobarbital, and rifampin mayqthe formation
of a toxic metabolite and mayqrisk of toxicity.
qmyelosuppression with other antineoplastics or radiation
therapy. Toxicity may beqby allopurinol or
phenobarbital. Maypantibody response to andq
risk of adverse reactions from live-virus vaccines.
Drug-Food: Grapefruit juice mayqlevels; avoid
concurrent use.
Route/Dosage
Other Regimens are Used
IV (Adults): 1.2 g/m2/day for 5 days; coadminister
with mesna. May repeat cycle q 3 wk.
Availability (generic available)
Powder for injection (requires reconstitution): 1
g/vial, 3 g/vial. Solution for injection: 50 mg/mL.
idaruCIZUmab (eye-da-roo-siz-ue-mab ) Praxbind
Indications
To counteract the anticoagulant effect of dabigatran for
emergency surgery/urgent procedures or life-threatening
uncontrolled bleeding.
Action
Human monoclonal antibody fragment (Fab) that selectively
binds to dabigatran and its metabolites, preventing
its binding to thrombin and negating its anticoagulant
effects. Does not reverse any other
anticoagulants. Therapeutic Effects: Reversal of
the anticoagulant effect of dabigatran.
Pharmacokinetics
Absorption: IV administration results in complete
bioavailability.
Distribution: Unknown.
Metabolism and Excretion: Biodegraded to
smaller molecules. 60% excreted in urine, remainder
via protein catabolism primarily in the kidneys.
Half-life: 10.3 hr.
TIME/ACTION PROFILE
ROUTE ONSET PEAK DURATION
IV immediate unknown 24 hr
Contraindications/Precautions
Contraindicated in: None noted.
Use Cautiously in: Geri: Elderly patients may be
more sensitive to drug effects; OB: Safety not established.
Consider maternal benefits and fetal risks; Lactation:
Safety not established, consider beneficial effects
of breast feeding and possible adverse effects in infant;
Pedi: Safety and effectiveness not established.
Exercise Extreme Caution in: Hereditary fructose
intolerance (risk of serious adverse reactions due
to sorbitol excipient); History of serious hypersensivity
(including anaphylactoid reactions) to idarucizumab.
Adverse Reactions/Side Effects
CNS: delerium. CV: THROMBOEMBOLISM. GI: constipation.
F and E: hypokalemia. Misc: hypersensitivity
reactions, fever.
Interactions
Drug-Drug: None noted.
Route/Dosage
IV (Adults): 5 g as single dose.
Availability
Solution for injection (contains sorbitol): 2.5 g/
50 mL single-use vial.
idaruCIZUmab (eye-da-roo-siz-ue-mab ) Praxbind
Indications
To counteract the anticoagulant effect of dabigatran for
emergency surgery/urgent procedures or life-threatening
uncontrolled bleeding.
Action
Human monoclonal antibody fragment (Fab) that selectively
binds to dabigatran and its metabolites, preventing
its binding to thrombin and negating its anticoagulant
effects. Does not reverse any other
anticoagulants. Therapeutic Effects: Reversal of
the anticoagulant effect of dabigatran.
Pharmacokinetics
Absorption: IV administration results in complete
bioavailability.
Distribution: Unknown.
Metabolism and Excretion: Biodegraded to
smaller molecules. 60% excreted in urine, remainder
via protein catabolism primarily in the kidneys.
Half-life: 10.3 hr.
TIME/ACTION PROFILE
ROUTE ONSET PEAK DURATION
IV immediate unknown 24 hr
Contraindications/Precautions
Contraindicated in: None noted.
Use Cautiously in: Geri: Elderly patients may be
more sensitive to drug effects; OB: Safety not established.
Consider maternal benefits and fetal risks; Lactation:
Safety not established, consider beneficial effects
of breast feeding and possible adverse effects in infant;
Pedi: Safety and effectiveness not established.
Exercise Extreme Caution in: Hereditary fructose
intolerance (risk of serious adverse reactions due
to sorbitol excipient); History of serious hypersensivity
(including anaphylactoid reactions) to idarucizumab.
Adverse Reactions/Side Effects
CNS: delerium. CV: THROMBOEMBOLISM. GI: constipation.
F and E: hypokalemia. Misc: hypersensitivity
reactions, fever.
Interactions
Drug-Drug: None noted.
Route/Dosage
IV (Adults): 5 g as single dose.
Availability
Solution for injection (contains sorbitol): 2.5 g/
50 mL single-use vial.
ibuprofen (eye-byoo-proe-fen) Advil, Advil Infants, Advil Junior Strength, Advil Migraine, Children’s Advil, Children’s Europrofen, Children’s Motrin, Motrin, Motrin IB, Motrin Infants Drops, Motrin Junior Strength, PediaCare IB Ibuprofen ibuprofen (injection) Caldolor, NeoProfen (ibuprofen lysine)
Indications
PO, IV: Treatment of: Mild to moderate pain, Fever.
PO: Treatment of: Inflammatory disorders including
rheumatoid arthritis (including juvenile) and osteoarthritis,
Dysmenorrhea. IV: Moderate to severe pain with
opioid analgesics. Closure of a clinically significant PDA
in neonates weighing 500–1500 g and 32 wk gestational
age (ibuprofen lysine only)
Action
Inhibits prostaglandin synthesis. Therapeutic Effects:
Decreased pain and inflammation. Reduction of fever.
Pharmacokinetics
Absorption: Oral formulation is well absorbed
(80%) from the GI tract; IV administration results in
complete bioavailability.
Distribution: Does not enter breast milk in significant
amounts.
Protein Binding: 99%.
Metabolism and Excretion: Mostly metabolized
by the liver; small amounts (1%) excreted unchanged
by the kidneys.
Half-life: Neonates: 26–43 hr; Children: 1–2 hr;
Adults: 2–4 hr.
TIME/ACTION PROFILE
ROUTE ONSET PEAK DURATION
PO (antipyretic) 0.5–2.5 hr 2–4 hr 6–8 hr
PO (analgesic) 30 min 1–2 hr 4–6 hr
PO (anti-inflammatory)
7 days 1–2 wk unknown
IV (analgesic) unknown unknown 6 hr
IV (antipyretic) within 2 hr 10–12 hr† 4–6 hr
† With repeated dosing.
Contraindications/Precautions
Contraindicated in: Hypersensitivity (cross-sensitivity
may exist with other NSAIDs, including aspirin);
Active GI bleeding or ulcer disease; Chewable tablets
contain aspartame and should not be used in patients
with phenylketonuria; Coronary artery bypass graft
(CABG) surgery; History of recent MI; Severe HF; OB:
Avoid after 30 wk gestation (may cause premature closure
of fetal ductus arteriosus); Pedi: Ibuprofen lysine:
Preterm neonates with untreated infection, congenital
heart disease where patency of PDA is necessary for
pulmonary or systemic blood flow, bleeding, thrombocytopenia,
coagulation defects, necrotizing enterocolitis,
significant renal dysfunction.
Use Cautiously in: Cardiovascular disease or risk
factors for cardiovascular disease (mayqrisk of serious
cardiovascular thrombotic events, MI, and stroke,
especially with prolonged use or use of higher doses);
avoid use in patients with recent MI or HF; Renal or hepatic
disease, dehydration, or patients on nephrotoxic
drugs (mayqrisk of renal toxicity); Aspirin triad patients
(asthma, nasal polyps, and aspirin intolerance);
can cause fatal anaphylactoid reactions; Chronic alcohol
use/abuse; Geri:qrisk of adverse reactions secondary
to age-relatedpin renal and hepatic function, concurrent
illnesses, and medications; Coagulation
disorders; OB: Use cautiously up to 30 wk gestation;
avoid after that; Lactation: Use cautiously; Pedi: Safety
not established for infants 6 mo (oral and IV Caldolor);
Hyperbilirubinemia in neonates (may displace bilirubin
from albumin-binding sites).
Exercise Extreme Caution in: History of GI
bleeding or GI ulcer disease.
Adverse Reactions/Side Effects
CNS: headache, dizziness, drowsiness, intraventricular
hemorrhage (ibuprofen lysine), psychic disturbances.
EENT: amblyopia, blurred vision, tinnitus. CV: HF,
MYOCARDIAL INFARCTION, STROKE, arrhythmias, edema,
hypertension. F and E: hyperkalemia. GI: GI BLEEDING,
HEPATITIS, constipation, dyspepsia, nausea, necrotizing
enterocolitis (ibuprofen lysine), vomiting, abdominal
discomfort. GU: cystitis, hematuria, renal
failure. Derm: EXFOLIATIVE DERMATITIS, STEVENS-JOHNSON
SYNDROME, TOXIC EPIDERMAL NECROLYSIS, rash, injection
site reaction. Hemat: anemia, blood dyscrasias,
prolonged bleeding time. Misc: allergic reactions
including ANAPHYLAXIS.
Interactions
Drug-Drug: May limit the cardioprotective effects of
low-dose aspirin. Concurrent use with aspirin mayp
effectiveness of ibuprofen. Additive adverse GI side effects
with aspirin, oral potassium, other NSAIDs,
corticosteroids, or alcohol. Chronic use with acetaminophen
mayqrisk of adverse renal reactions. May
peffectiveness of diuretics, ACE inhibitors, or other
antihypertensives. Mayqhypoglycemic effects of insulin
or oral hypoglycemic agents. Mayqserum
lithium levels and risk of toxicity.qrisk of toxicity
from methotrexate. Probenecidqrisk of toxicity
from ibuprofen.qrisk of bleeding with cefotetan,
corticosteroids, valproic acid, thrombolytics,
warfarin, and drugs affecting platelet function including
clopidogrel, abciximab, eptifibatide, or tirofiban.
qrisk of adverse hematologic reactions with
antineoplastics or radiation therapy.qrisk of
nephrotoxicity with cyclosporine.
Drug-Natural Products:qbleeding risk with, arnica,
chamomile, feverfew, garlic, ginger, ginkgo,
Panax ginseng, and others.
Route/Dosage
Analgesia
PO (Adults): Anti-inflammatory—400–800 mg 3–
4 times daily (not to exceed 3200 mg/day). Analgesic/
antidysmenorrheal/antipyretic—200–400 mg every
4–6 hr (not to exceed 1200 mg/day).
PO (Children 6 mo–12 yr): Anti-inflammatory—
30–50 mg/kg/day in 3–4 divided doses (maximum
dose: 2.4 g/day). Antipyretic—5 mg/kg for temperature
102.5F (39.17C) or 10 mg/kg for higher temperatures
(not to exceed 40 mg/kg/day); may be repeated
every 4–6 hr. Cystic fibrosis (unlabeled)—
20–30 mg/kg/day divided twice daily.
PO (Infants and Children): Analgesic—4–10 mg/
kg/dose every 6–8 hr.
IV (Adults): Analgesic—400–800 mg every 6 hr as
needed (not to exceed 3200 mg/day); Antipyretic—
400 mg initially, then 400 mg every 4–6 hr or 100–
200 mg every 4 hr as needed (not to exceed 3200 mg/
day).
IV (Children 12–17 yr): Analgesic and antipyretic—
400 mg every 4–6 hr as needed (not to exceed
2400 mg/day).
IV (Children 6 mo–12 yr): Analgesic and antipyretic—
10 mg/kg (not to exceed 400 mg) every 4–6
hr as needed (not to exceed 40 mg/kg/day or 2400 mg/
day whichever is less).
Pediatric OTC Dosing
PO (Children 11 yr/72–95 lb): 300 mg every 6–8
hr.
PO (Children 9–10 yr/60–71 lb): 250 mg every 6–
8 hr.
PO (Children 6–8 yr/48–59 lb): 200 mg every 6–
8 hr.
PO (Children 4–5 yr/36–47 lb): 150 mg every 6–
8 hr.
PO (Children 2–3 yr/24–35 lb): 100 mg every 6–
8 hr.
PO (Children 12–23 mo/18–23 lb): 75 mg every
6–8 hr.
PO (Infants 6–11 mo/12–17 lb): 50 mg every 6–8
hr.
PDA Closure
IV (Neonates Gestational age 32 weeks, 500–
1500 g): 10 mg/kg followed by two doses of 5 mg/kg
at 24 and 48 hr after initial dose.
Availability (generic available)
Tablets: 100 mgOTC, 200 mgOTC, 300 mg, 400 mg, 600
mg, 800 mg. Capsules (liquigels): 200 mgOTC. Chewable
tablets (fruit, grape, orange, and citrus flavor
): 50 mgOTC, 100 mgOTC. Oral suspension (fruit,
berry, grape flavor): 100 mg/5 mLOTC. Pediatric
drops (berry flavor): 50 mg/1.25 mLOTC. Solution
for injection: 100 mg/mL (Caldolor), 17.1 mg/mL as
lysine, 10 mg/mL as ibuprofen base (Neoprofen). In
combination with: decongestantsOTC, hydrocodone
(Reprexain), famotidine (Duexis). See Appendix B.
ibandronate (i-ban-dro-nate) Boniva
Indications
Treatment/prevention of postmenopausal osteoporosis.
Action
Inhibits resorption of bone by inhibiting osteoclast activity.
Therapeutic Effects: Reversal/prevention of
progression of osteoporosis with decreased fractures.
Pharmacokinetics
Absorption: 0.6% absorbed following oral administration
(significantlypby food).
Distribution: Rapidly binds to bone.
Protein Binding: 90.9–99.5%.
Metabolism and Excretion: 50–60% excreted in
urine; unabsorbed drug is eliminated in feces.
Half-life: PO—10–60 hr; IV—4.6–25.5 hr.
TIME/ACTION PROFILE
ROUTE ONSET PEAK DURATION
PO unknown 0.5–2 hr up to 1 mo
IV unknown 3 hr up to 3 mo
Contraindications/Precautions
Contraindicated in: Hypersensitivity; Abnormalities
of the esophagus which delay esophageal emptying
(i.e. strictures, achalasia); Uncorrected hypocalcemia;
Inability to stand/sit upright for at least 60 min; CCr
30 mL/min.
Use Cautiously in: History of upper GI disorders;
Concurrent use of NSAIDs or aspirin; Invasive dental
procedures, cancer, receiving chemotherapy, corticosteroids,
or angiogenesis inhibitors, poor oral hygiene,
periodontal disease, dental disease, anemia, coagulopathy,
infection, or poorly-fitting dentures (mayqrisk of
jaw osteonecrosis); OB: Use only if potential benefit
outweighs risks to mother and fetus; Lactation: Lactation;
Pedi: Children 18 yr (safety not established);
Geri: Consider age relatedpin body mass, renal and
hepatic function, concurrent disease states and drug
therapy.
Adverse Reactions/Side Effects
GI: diarrhea, dyspepsia, dysphagia, esophageal cancer,
esophagitis, esophageal/gastric ulcer. MS: musculoskeletal
pain, pain in arms/legs, femur fractures, osteonecrosis
(primarily of jaw). Derm: ERYTHEMA MULTIFORME,
STEVENS-JOHNSON SYNDROME. Resp: asthma
exacerbation. Misc: ANAPHYLAXIS, injection site reactions.
Interactions
Drug-Drug: Calcium-, aluminum-, magnesium-,
and iron- containing products, including antacidsp
absorption (ibandronate should be taken 60 min before).
Concurrent use of NSAIDs including aspirin,
mayqrisk of gastric irritation.
Drug-Food: Milk and other foodspabsorption.
Route/Dosage
PO (Adults): 150 mg once monthly.
IV (Adults): 3mg every 3 mo.
Availability (generic available)
Tablets: 150 mg. Injection: 3 mg/3 mL in prefilled
single-use syringe.
hydroxyprogesterone caproate (hye-drox-ee-pro-jess-te-rone kap-roe-ate) Makena
Indications
Topthe risk of preterm birth in women with a singleton
pregnancy who have a history of previous singleton
preterm birth.
Action
A synthetic analog of progesterone. Produces secretory
changes in the endometrium.qs basal temperature.
Produces changes in the vaginal epithelium. Relaxes
uterine smooth muscle. Stimulates mammary alveolar
growth. Inhibits pituitary function. Action in reducing
risk of recurrent preterm birth is unknown. Therapeutic
Effects:prisk of preterm birth in women at
risk.
Pharmacokinetics
Absorption: Slowly absorbed following IM administration.
Distribution: Unknown.
Protein Binding: Extensively bound to plasma proteins.
Metabolism and Excretion: Extensively metabolized
by the liver.
Half-life: 7.8 days.
TIME/ACTION PROFILE (blood levels)
ROUTE ONSET PEAK DURATION
IM unknown 4.6 days 7 days
Contraindications/Precautions
Contraindicated in: Hypersensitivity to hydroxyprogesterone
or castor oil; History of or known thrombosis/
thromboembolic disorder; History of or known/
suspected breast cancer or other hormone-sensitive
cancer; Unexplained abnormal vaginal bleeding unrelated
to pregnancy; Cholestatic jaundice of pregnancy;
Benign/malignant liver tumors or active liver disease;
Uncontrolled hypertension.
Use Cautiously in: Risk factors for thromboembolic
disorders (mayqrisk); Diabetes mellitus or risk
factors for diabetes mellitus (may impair glucose tolerance);
History of preeclampsia, epilepsy, cardiac or renal
impairment (may be adversely affected by fluid retention);
History of depression (may worsen); Safe and
effective use in children 16 yr has not been established.
Adverse Reactions/Side Effects
CNS: depression. CV: hypertension. GI: diarrhea,
jaundice, nausea. Derm: urticaria, pruritus. F and
E: fluid retention. Hemat: THROMBOEMBOLISM. Local:
injections site reactions. Misc: allergic reactions
including ANGIOEDEMA.
Interactions
Drug-Drug: Mayqmetabolism andpblood levels
and effectiveness of drugs metabolized by the
CYP1A2, CYP2A6, and CYP2B6 enzyme systems.
Route/Dosage
IM (Adults): 250 mg once weekly starting between 16
wks, 0 days and 20 wks, 6 days continuing until wk 37
of gestation or delivery, whichever occurs first.
Availability
Solution for IM injection (contains castor oil):
1250 mg/5 mL vial (250 mg/mL).
hydroxychloroquine, Plaquenil
Indications
Treatment of uncomplicated malaria in geographic areas
where chloroquine-resistance is not reported. Prophylaxis
of malaria in geographic areas where chloroquine-
resistance is not reported. Treatment of acute
and chronic rheumatoid arthritis. Treatment of chronic
discoid lupus erythematosus and systemic lupus erythematosus.
Action
Inhibits protein synthesis in susceptible organisms by
inhibiting DNA and RNA polymerase. Therapeutic
Effects: Death of plasmodia responsible for causing
malaria. Also has anti-inflammatory properties. Spectrum:
Active against chloroquine-sensitive strains of:
Plasmodium falciparum, Plasmodium malariae, a-
Plasmodium ovale, and Plasmodium vivax.
Pharmacokinetics
Absorption: Highly variable (31–100%) following
oral administation.
Distribution: Widely distributed; high concentrations
in RBCs; crosses the placenta; excreted into breast
milk.
Metabolism and Excretion: Partially metabolized
by the liver to active metabolites; partially excreted unchanged
by the kidneys.
Half-life: 40 days.
TIME/ACTION PROFILE (blood levels)
ROUTE ONSET PEAK DURATION
PO rapid† 1–2 hr days–weeks
†Onset of antirheumatic action may take 6 wk.
Contraindications/Precautions
Contraindicated in: Hypersensitivity to hydroxychloroquine
or chloroquine; Previous visual damage
from hydroxychloroquine or chloroquine.
Use Cautiously in: Concurrent use of hepatotoxic
drugs; Hepatic impairment or alcoholism; Use of high
doses (5 mg/kg base), duration of use 5 yr, renal
impairment, concurrent use of tamoxifen or macular
disease (qrisk of retinopathy); G6PD deficiency; Psoriasis;
Porphyria; Bone marrow depression; Obesity (determine
dose by ideal body weight); OB, Lactation:
Avoid use unless treating/preventing malaria or treating
amebic abscess; Geri:prenal function mayqrisk of
adverse reactions; Pedi: Safety and effectiveness for
chronic use not established.
Adverse Reactions/Side Effects
CNS: SEIZURES, SUICIDAL THOUGHTS/BEHAVIORS, aggressiveness,
anxiety, dizziness, fatigue, headache, irritability,
nightmares, personality changes, psychoses.
EENT: corneal deposits, nystagmus, retinopathy, tinnitus,
vertigo, visual disturbances. CV: HF, TORSADE DE
POINTES, heart block, QT interval prolongation. Endo:
hypoglycemia. GI: HEPATOTOXICITY, abdominal pain,
anorexia, diarrhea,qliver enzymes, nausea, vomiting.
Derm: DRUG REACTION WITH EOSINOPHILIA AND SYSTEMIC
SYMPTOMS (DRESS), ERYTHEMA MULTIFORME, STEVENS-
JOHNSON SYNDROME, TOXIC EPIDERMAL NECROLYSIS,
acute generalized exanthematous pustulosis, alopecia,
hair color changes, hyperpigmentation, photosensitivity,
pruritus, rash, urticaria. Hemat: AGRANULOCYTOSIS,
APLASTIC ANEMIA, leukopenia, thrombocytopenia. Metab:
pweight. Neuro: ataxia, dyskinesia, dystonia,
neuromyopathy, peripheral neuritis, tremor. Resp:
PULMONARY HYPERTENSION, bronchospasm. Misc: ANGIOEDEMA.
Interactions
Drug-Drug: Concurrent use of other QT intervalprolonging
drugs mayqrisk of torsade de pointes.
Mayqthe risk of hepatotoxicity when administered with
hepatotoxic drugs. Mayqrisk of hypoglycemia when
used with antidiabetic agents. Use with mefloquine
mayqrisk of seizures. Antacids may bind to andpthe
absorption of hydroxychloroquine; separate administration
by 4 hr. Cimetidine mayqlevels; avoid concurrent
use. Urinary acidifiers mayqrenal excretion.
Mayqlevels of digoxin or cyclosporine.
Route/Dosage
200 mg hydroxychloroquine sulfate155 mg of hydroxychloroquine
base.
Malaria
PO (Adults): Prophylaxis—400 mg sulfate (310 mg
base) once weekly; start 2 wk prior to entering malarious
area; continue for 4 wk after leaving area. Treatment—
800 mg sulfate (620 mg base), then 400 mg
sulfate (310 mg base) at 6 hr, 24 hr, and 48 hr after
initial dose.
PO (Children 31 kg): Prophylaxis—6.5 mg/kg
sulfate (5 mg/kg base) (not to exceed 400 mg sulfate
[310 mg base]) once weekly; start 2 wk prior to entering
malarious area; continue for 4 wk after leaving
area. Treatment—13 mg/kg sulfate (10 mg/kg base)
(not to exceed 800 mg sulfate [620 mg base]) initially,
then 6.5 mg/kg sulfate (5 mg/kg base) (not to exceed
400 mg sulfate [310 mg base]) at 6 hr, 24 hr, and 48
hr after initial dose.
Rheumatoid Arthritis
PO (Adults): 400–600 mg sulfate (310–465 mg
base) per day in 1–2 divided doses; once adequate response
obtained, maypdose to maintenance dose of
200–400 mg sulfate (155–310 mg base) per day in
1–2 divided doses.
Lupus Erythematosus
PO (Adults): 200–400 mg sulfate (155–310 mg
base) per day in 1–2 divided doses.
Availability (generic available)
Tablets: 200 mg sulfate (155 mg base). Cost: Generic—$
14.88/100.
HYDROmorphone (hye-droe-mor-fone) Dilaudid, Dilaudid-HP, Exalgo, Hydromorph Contin, Jurnista
Indications
Moderate to severe pain (alone and in combination
with nonopioid analgesics). Moderate to severe chronic
pain in opioid-tolerant patients requiring use of daily,
around-the-clock long-term opioid treatment and for
which alternative treatment options are inadequate (extended-
release). Antitussive (lower doses).
Action
Binds to opiate receptors in the CNS. Alters the perception
of and response to painful stimuli while producing
generalized CNS depression. Suppresses the cough reflex
via a direct central action. Therapeutic Effects:
Decrease in moderate to severe pain. Suppression
of cough.
Pharmacokinetics
Absorption: Well absorbed following oral, rectal,
subcut, and IM administration. Extended-release product
results in an initial release of drug, followed by a
second sustained phase of absorption.
Distribution: Widely distributed. Crosses the placenta;
enters breast milk.
Metabolism and Excretion: Mostly metabolized
by the liver.
Half-life: Oral (immediate-release), or injection—
2–4 hr; Oral (extended-release)—8–15 hr.
TIME/ACTION PROFILE (analgesic effect)
ROUTE ONSET PEAK DURATION
PO-IR 30 min 30–90 min 4–5 hr
PO-ER unknown unknown unknown
Subcut 15 min 30–90 min 4–5 hr
IM 15 min 30–60 min 4–5 hr
IV 10–15 min 15–30 min 2–3 hr
Rect 15–30 min 30–90 min 4–5 hr
Contraindications/Precautions
Contraindicated in: Hypersensitivity; Some products
contain bisulfites and should be avoided in patients
with known hypersensitivity; Severe respiratory depression
(in absence of resuscitative equipment) (extended-
release only); Acute or severe bronchial asthma
(extended-release only); Paralytic ileus (extended-release
only); Acute, mild, intermittent, or postoperative
pain (extended-release only); Prior GI surgery or narrowing
of GI tract (extended-release only); Opioid nontolerant
patients (extended-release only); Severe hepatic
impairment (extended-release only).
Use Cautiously in: Head trauma;qintracranial
pressure; Severe pulmonary disease; Moderate or severe
renal disease (extended-release only) (doseprecommended);
Moderate hepatic impairment (extendedrelease
only) (doseprecommended); Hypothyroidism;
Seizure disorder; Adrenal insufficiency; Alcoholism;
Undiagnosed abdominal pain; Prostatic hypertrophy;
Biliary tract disease (including pancreatitis); OB: Labor
and delivery; OB, Lactation: Avoid chronic use; prolonged
use of opioids during pregnancy can result in
neonatal opioid withdrawal syndrome; Geri: Geriatric
or debilitated patients (qrisk of respiratory depression;
dosepsuggested).
Adverse Reactions/Side Effects
CNS: confusion, sedation, dizziness, dysphoria, euphoria,
floating feeling, hallucinations, headache, unusual
dreams. EENT: blurred vision, diplopia, miosis.
Resp: RESPIRATORY DEPRESSION. CV: hypotension,
bradycardia. Endo: adrenal insufficiency. GI: constipation,
dry mouth, nausea, vomiting. GU: urinary retention.
Derm: flushing, sweating. Misc: physical dependence,
psychological dependence, tolerance.
Interactions
Drug-Drug: Exercise extreme caution with MAO inhibitors
(may produce severe, unpredictable reactions—
reduce initial dose of hydromorphone to 25%
of usual dose, discontinue MAO inhibitors 2 wk prior to
hydromorphone). Use with benzodiazepines or
other CNS depressants including other opioids,
non-benzodiazepine sedative/hypnotics, anxiolytics,
general anesthetics, muscle relaxants, antipsychotics,
and alcohol may cause profound sedation,
respiratory depression, coma, and death; reserve
concurrent use for when alternative treatment options
are inadequate. Administration of partial antagonists
(buprenorphine, butorphanol, nalbuphine, or
pentazocine) may precipitate opioid withdrawal in
physically dependent patients. Nalbuphine or pentazocine
maypanalgesia. Drugs that affect serotonergic
neurotransmitter systems, including tricyclic antidepressants,
SSRIs, SNRIs, MAO inhibitors, TCAs,
tramadol, trazodone, mirtazapine, 5–HT3 receptor
antagonists, linezolid, methylene blue, and
triptansqrisk of serotonin syndrome.
Drug-Natural Products: Concomitant use of
kava-kava, valerian, chamomile, or hops canq
CNS depression.
Route/Dosage
Doses depend on level of pain and tolerance. Larger
doses may be required during chronic therapy.
Analgesic
PO (Adults 50 kg): Immediate-release—4–8 mg
every 3–4 hr initially (some patients may respond to doses as small as 2 mg initially); or once 24-hr opioid
requirement is determined, convert to extended-release
by administering total daily oral dose once daily.
PO (Adults and Children 50 kg): 0.06 mg/kg
every 3–4 hr initially, younger children may require
smaller initial doses of 0.03 mg/kg. Maximum dose 5
mg.
IV, IM, Subcut (Adults 50 kg): 1.5 mg every 3–4
hr as needed initially; may beq.
IV, IM, Subcut (Adults and Children 50 kg):
0.015 mg/kg mg every 3–4 hr as needed initially; may
beq.
IV (Adults): Continuous infusion (unlabeled)—
0.2–3 mg/hr depending on previous opioid use. An initial
bolus of twice the hourly rate in mg may be given
with subsequent breakthrough boluses of 50–100% of
the hourly rate in mg.
Rect (Adults): 3 mg every 6–8 hr initially as needed.
Hepatic Impairment
PO (Adults): Moderate hepatic impairment (extended–
release)—pinitial dose by 75%.
Renal Impairment
PO (Adults): Moderate renal impairment (extended–
release)—pinitial dose by 50%; Severe renal
impairment (extended–release)—pinitial dose
by 75%.
Antitussive
PO (Adults and Children 12 yr): 1 mg every 3–4
hr.
PO (Children 6–12 yr): 0.5 mg every 3–4 hr.
Availability (generic available)
Immediate-release tablets: 2 mg, 4 mg, 8 mg. Extended-
release tablets (abuse-deterrent): 4
mg, 8 mg, 12 mg, 16 mg, 32 mg. Controlled-release
capsules: 3 mg, 4.5 mg, 6 mg, 9 mg, 12
mg, 18 mg, 24 mg, 30 mg. Oral solution: 1
mg/mL. Injection: 1 mg/mL, 2 mg/mL, 4 mg/mL, 10
mg/mL. Suppositories: 3 mg.
HYDROcodone (hye-droe-koe-done) Hysingla ER, Zohydro ER HYDROcodone/ acetaminophen Anexsia, Norco HYDROcodone/ibuprofen Reprexain
Indications
Extended-release product: Management of pain that
is severe enough to warrant daily, around-the-clock,
long-term opioid treatment where alternative treatment
options are inadequate. Combination products:
Management of moderate to severe pain. Antitussive
(usually in combination products with decongestants).
Action
Bind to opiate receptors in the CNS. Alter the perception
of and response to painful stimuli while producing
generalized CNS depression. Suppress the cough reflex
via a direct central action. Therapeutic Effects:
Decrease in severity of moderate pain. Suppression of
the cough reflex.
Pharmacokinetics
Absorption: Well absorbed following oral administration.
Distribution: Unknown.
Metabolism and Excretion: Mostly metabolized
by the liver; eliminated in the urine (50–60% as metabolites,
10% as unchanged drug).
Half-life: 2.2 hr; Extended-release—8 hr.
TIME/ACTION PROFILE (analgesic effect)
ROUTE ONSET PEAK DURATION
PO 10–30 min 30–60 min 4–6 hr
PO-ER unknown unknown unknown
Contraindications/Precautions
Contraindicated in: Hypersensitivity to hydrocodone
(cross-sensitivity may exist to other opioids); Significant
respiratory depression; Paralytic ileus; Acute or
severe bronchial asthma or hypercarbia; Congenital
long QT syndrome (Hysingla only); Hypersensitivity to
acetaminophen/ibuprofen (for combination products);
Ibuprofen-containing products should be avoided in
patients with bleeding disorders or thrombocytopenia;
Acetaminophen-containing products should be avoided
in patients with severe hepatic or renal disease; Ibuprofen-
containing products should be avoided in patients
undergoing coronary artery bypass graft surgery; OB,
Lactation: Avoid chronic use; Products containing alcohol,
aspartame, saccharin, sugar, or tartrazine (FDC
yellow dye #5) should be avoided in patients who have
hypersensitivity or intolerance to these compounds.
Use Cautiously in: Head trauma;qintracranial
pressure; Severe renal, hepatic, or pulmonary disease;
Cardiovascular disease (ibuprofen-containing products
only); History of peptic ulcer disease (ibuprofen-containing
products only); Alcoholism; Difficulty swallowing;
Patients with undiagnosed abdominal pain; Prostatic
hyperplasia; OB: Labor and delivery; OB, Lactation:
Avoid chronic use; prolonged use of opioids during
pregnancy can result in neonatal opioid withdrawal
syndrome; Geri: Geriatric or debilitated patients (initial
doseprequired; more prone to CNS depression, constipation).
Adverse Reactions/Side Effects
Noted for hydrocodone only; see acetaminophen/ibuprofen
monographs for specific information on individual
components.
CNS: confusion, dizziness, sedation, euphoria, hallucinations,
headache, unusual dreams. EENT: blurred vision,
diplopia, miosis. Resp: respiratory depression.
CV: hypotension, bradycardia, QT interval prolongation
(Hysingla only). GI: constipation, dyspepsia, nausea,
choking, dysphagia, esophageal obstruction, vomiting.
GU: urinary retention. Endo: adrenal
insufficiency. Derm: sweating. Misc: physical dependence,
psychological dependence, tolerance.
Interactions
Drug-Drug: Use with extreme caution in patients receiving
MAO inhibitors; may produce severe, unpredictable
reactions—do not use within 14 days of each
other. Concurrent use of CYP3A4 inhibitors including
ritonavir, ketoconazole, itraconazole, fluconazole,
clarithromycin, erythromycin, nefazodone,
diltiazem, verapamil, nelfinavir, and fosamprenavirqlevels
and risk of opioid toxicity; careful monitoring
during initiation, dose changes, or discontinuation
of the inhibitor is recommended. Concurrent use with
CYP3A4 inducers including barbiturates, carbamazepine,
efavirenz, corticosteroids, modafinil,
nevirapine, oxcarbazepine, phenobarbital, phenytoin,
rifabutin, or rifampin maypfentanyl levels
and analgesia; if inducers are discontinued or dosage p,
patients should be monitored for signs of opioid toxicity
and necessary dose adjustments should be made.
Use with benzodiazepines or other CNS depressants
including otheropioids, non-benzodiazepine
sedative/hypnotics, anxiolytics, general anesthetics,
muscle relaxants, antipsychotics, and alcohol
may cause profound sedation, respiratory depression,
coma, and death; reserve concurrent use for when alternative
treatment options are inadequate. Administration
of partial antagonist opioids (buprenorphine,
butorphanol, nalbuphine, or pentazocine) mayp
analgesia or precipitate opioid withdrawal in physically
dependent patients. Anticholinergic drugs mayq
risk of urinary retention and constipation. Drugs that
affect serotonergic neurotransmitter systems, including
tricyclic antidepressants, SSRIs, SNRIs, MAO inhibitors,
TCAs, tramadol, trazodone, mirtazapine,
5–HT3 receptor antagonists, linezolid,
methylene blue, and triptansqrisk of serotonin syndrome.
Drug-Natural Products: Concomitant use of
kava-kava, valerian, skullcap, chamomile, or
hops canqCNS depression.
Route/Dosage
PO (Adults): Analgesic—2.5–10 mg q 3–6 hr as
needed; if using combination products, acetaminophen
dosage should not exceed 4 g/day and should not exceed
5 tablets/day of ibuprofen-containing products;
Antitussive—5 mg q 4–6 hr as needed; Extended-release
(Zohydro ER)—10 mg q 12 hr; mayqas needed
in increments of 10 mg q 12 hr q 3–7 days; Extendedrelease
(Hysingla)—20 mg once daily; mayqas
needed in increments of 10–20 mg/day q 3–5 days.
PO (Children): Analgesic (1–13 yr)—0.1–0.2 mg/
kg q 3–4 hr. Antitussive —0.6 mg/kg/day divided q
6–8 hr; (maximum doses 2 yr: 1.25 mg/dose; 2–12
yr: 5 mg/dose; 12 yr: 10 mg/dose).
Renal Impairment
PO (Adults): CCr 45 mL/min—Extended-release
(Hysingla):pinitial dose by 50%.
Hepatic Impairment
PO (Adults): Extended-release (Hysingla)—pinitial
dose by 50%.
Availability
Hydrocodone (generic available)
Extended-release capsules (Zohydro ER) (abuse
deterrent): 10 mg, 15 mg, 20 mg, 30 mg, 40 mg, 50
mg. Extended-release tablets (Hysingla ER)
(abuse deterrent): 20 mg, 30 mg, 40 mg, 60 mg, 80
mg, 100 mg, 120 mg. Syrup: 1 mg/mL. In combination
with: chlorpheniramine (Tussicaps, Tussionex,
Vituz); chlorpheniramine and pseudoephedrine
(Zutripro); guaifenesin (Flowtuss, Obredon); guaifenesin
and pseudoephedrine (Hycofenix); pseudoephedrine
(Rezira). See Appendix B.
Hydrocodone/Acetaminophen (generic
available)
Tablets: 2.5 mg hydrocodone/325 mg acetaminophen,
5 mg hydrocodone/325 mg acetaminophen (Anexsia 5/
325, Norco), 7.5 mg hydrocodone/325 mg acetaminophen
(Anexsia 7.5/325, Norco), 10 mg hydrocodone/
325 mg acetaminophen (Norco). Cost: Generic—5
mg/325 mg $15.08/100, 7.5 mg/325 mg $30.93/100,
10 mg/325 mg $41.59/100. Elixir/oral solution: 7.5
mg hydrocodone plus 325 mg acetaminophen/15 mL,
10 mg hydrocodone plus 325 mg acetaminophen/15
mL. Cost: Generic—$58.12/473 mL.
Hydrocodone/Ibuprofen (generic available)
Tablets: 2.5 mg hydrocodone/200 mg ibuprofen (Reprexain),
5 mg hydrocodone/200 mg ibuprofen, 7.5
mg hydrocodone/200 mg ibuprofen, 10 mg hydrocodone/
200 mg ibuprofen (Reprexain). Cost: Generic—
7.5 mg/200 mg $48.40/100.
hydralazine/isosorbide dinitrate (hye-dral-a-zeen eye-so-sor-bide di-ni-trate) BiDil
Indications
Management of heart failure in black patients.
Action
BiDil is a fixed-dose combination of isosorbide dinitrate,
a vasodilator with effects on both arteries and
veins, and hydralazine, a predominantly arterial vasodilator.
Therapeutic Effects: Improved survival, increased
time to hospitalization and decreased symptoms
of heart failure in black patients.
Pharmacokinetics
See pharmacokinetic sections in hydralazine and isosorbide
dinitrate monographs of Davis’s Drug Guide for
Nurses for more information.
Absorption: Hydralazine—10–26% absorbed in
HF patients, absorption can be saturated leading to
largeqin absorption with higher doses; isosorbide
dinitrate—variable absorbed (10–90%) reflecting
first-pass hepatic metabolism.
Distribution: Hydralazine—widely distributed,
crosses the placenta, minimal amounts in breast milk;
isosorbide dinitrate—accumulates in muscle and venous
wall.
Metabolism and Excretion: Hydralazine—
mostly metabolized by GI mucosa and liver; isosorbide
dinitrate—undergoes extensive first-pass metabolism
in the liver, mostly metabolized by the liver, some metabolites
are vasodilators.
Half-life: Hydralazine—4 hr; isosorbide dinitrate—
2 hr.
TIME/ACTION PROFILE (effect on BP)
ROUTE ONSET PEAK DURATION
hydralazine 45 min 2 hr 2–4 hr
isosorbide 15–40 min unknown 4 hr
Contraindications/Precautions
Contraindicated in: Hypersensitivity to either component;
Concurrent use of PDE-5 inhibitor (avanafil,
sildenafil, tadalafil, vardenafil) or riociguat.
Use Cautiously in: Severe renal/hepatic disease
(dose modification may be necessary); Head trauma or
cerebral hemorrhage; Geri: Start with lower doses; OB:
May compromise maternal/fetal circulation; Lactation:
Safety not established; Pedi: Safety not established.
Adverse Reactions/Side Effects
Hydralazine
CNS: dizziness, drowsiness, headache. CV: tachycardia,
angina, arrhythmias, edema, orthostatic hypotension.
GI: diarrhea, nausea, vomiting. Derm: rash. F
and E: sodium retention. MS: arthralgias, arthritis.
Neuro: peripheral neuritis. Misc: drug-induced lupus
syndrome.
Isosorbide Dinitrate
CNS: dizziness, headache, apprehension, weakness.
CV: hypotension, tachycardia, paradoxic bradycardia,
syncope. GI: abdominal pain, nausea, vomiting. Misc:
cross-tolerance, flushing, tolerance.
Interactions
Drug-Drug: Concurrent use of avanafil, sildenafil,
tadalafil, or vardenafil may result in severe hypotension;
concurrent use contraindicated. Concurrent use
of riociguat may result in severe hypotension; concurrent
use contraindicated.qrisk of hypotension with
other antihypertensives, acute ingestion of alcohol,
and phenothiazines. MAO inhibitors may exaggerate
hypotension. Maypthe pressor response to epinephrine.
Beta blockersptachycardia from hydralazine
(therapy may be combined for this reason).
Metoprolol and propranolol mayqhydralazine levels.
Hydralazineqlevels of metoprolol and propranolol.
Route/Dosage
PO (Adults): 1 tablet 3 times daily, may beqto 2 tablets
3 times daily.
Availability
Tablets: hydralazine 37.5 mg/isosorbide dinitrate 20 mg.
hydrALAZINE (hye-dral-a-zeen) Apresoline
Indications
Moderate to severe hypertension (with a diuretic). Unlabeled
Use: HF unresponsive to conventional therapy
with digoxin and diuretics.
Action
Direct-acting peripheral arteriolar vasodilator. Therapeutic
Effects: Lowering of BP in hypertensive patients
and decreased afterload in patients with HF.
Pharmacokinetics
Absorption: Rapidly absorbed following oral administration;
well absorbed from IM sites.
Distribution: Widely distributed. Crosses the placenta;
enters breast milk in minimal concentrations.
Metabolism and Excretion: Mostly metabolized
by the GI mucosa and liver by N-acetyltransferase
(rate of acetylation is genetically determined [slow acetylators
haveqhydralazine levels andqrisk of toxicity;
fast acetylators havephydralazine levels andpresponse]).
Half-life: 2–8 hr.
TIME/ACTION PROFILE (antihypertensive
effect)
ROUTE ONSET PEAK DURATION
PO 45 min 2 hr 2–4 hr
IM 10–30 min 1 hr 3–8 hr
IV 5–20 min 15–30 min 2–6 hr
Contraindications/Precautions
Contraindicated in: Hypersensitivity; Some products
contain tartrazine and should be avoided in patients
with known intolerance.
Use Cautiously in: Cardiovascular or cerebrovascular
disease; Severe renal and hepatic impairment
(dose modification may be necessary); OB, Lactation:
Has been used safely during pregnancy.
Adverse Reactions/Side Effects
CNS: dizziness, drowsiness, headache. CV: tachycardia,
angina, arrhythmias, edema, orthostatic hypotension.
GI: diarrhea, nausea, vomiting. Derm: rash.
MS: arthralgias, arthritis. Neuro: peripheral neuropathy.
Misc: drug-induced lupus syndrome.
Interactions
Drug-Drug:qhypotension with acute ingestion of
alcohol, other antihypertensives, or nitrates. MAO
inhibitors may exaggerate hypotension. Mayppressor
response to epinephrine. NSAIDs maypantihypertensive
response. Beta blockersptachycardia
from hydralazine (therapy may be combined for this
reason). Metoprolol and propranololqlevels.q
levels of metoprolol and propranolol.
Route/Dosage
PO (Adults): Hypertension—10 mg 4 times daily initially.
After 2–4 days mayqto 25 mg 4 times daily for
the rest of the 1st week; may thenqto 50 mg 4 times
daily (up to 300 mg/day). Once maintenance dose is
established, twice-daily dosing may be used. HF—25–
37.5 mg 4 times daily; may bequp to 300 mg/day in
3–4 divided doses.
PO (Children 1 mo): Initial—0.75–1 mg/kg/day
in 2–4 divided doses, not to exceed 25 mg/dose; may
qgradually to 5 mg/kg/day in infants and 7.5 mg/kg/
day in children (not to exceed 200 mg/day) in 2–4 divided
doses.
IM, IV (Adults): Hypertension—5–40 mg repeated
as needed. Eclampsia—5mg q 15–20min; if no response
after a total of 20 mg, consider an alternative
agent.
IM, IV (Children 1mo): Initial—0.1–0.2 mg/kg/
dose (not to exceed 20 mg) every 4–6 hr as needed,
up to 1.7–3.5 mg/kg/day in 4–6 divided doses.
Availability (generic available)
Tablets: 10 mg, 25 mg, 50 mg, 100 mg. Injection: 20
mg/mL. In combination with: isosorbide dinitrate
(BiDil). See Appendix B.
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